A large number of patients with both neoplastic and non-neoplastic inappropriate TSH production have been identified using novel diagnostic methods. The molecular basis for these disorders is under investigation and new therapeutic approaches are being explored. Inappropriate TSH action has been discovered in patients with central hypothyroidism. The biologically inactive TSH in this disease results from impaired binding to its receptor and the bioactivity can be restored by chronic treatment with thyrotropin-releasing hormone. In rats, various hormones regulate TSH bioactivity, metabolic clearance and targeting; studies with chemically deglycosylated TSH suggest that these effects are mediated by changes in carbohydrate structure. Functional primary cultures of human and porcine thyroid follicies are being developed to define the mechanisms of action of various thyrotropic hormones and immunoglobulins.